Those of our investigations which involve controlled dietary restriction have now arrived at the stage where we are able to obtain a striking prolongation of the life-span of an already long-lived strain of mouse. This prolongation is accompanied by a relative preservation into advanced age of immune response capacity. The main thrust of our renewal request is to further capitalize upon this system as follows: 1. Additional dietary manipulation, including improved diets plus in one calorically restricted cohort a gradually imposed decrease in the ratio of protein to carbohydrate as the animals age (which we believe will lead to further prolongation); the inclusion of diets containing a high level of polyunsaturated fatty acids (which are immunoinhibitory). 2. Further studies of the immune system of dietarily restricted and of control mice in relation to age: the mixed lymphocyte reaction, "synergy," responses to mitogens, cell-mediated lymphocytoxicity, suppressor cells, self/non-self discrimination as detected in responses to TNP-modified xenogeneic, allogeneic, and syngeneic red blood cells and lymphocytes, percentages of lymphoid cell subpopulations as detected by anti-Ly antisera. 3. Autoantibody levels. 4. Psychological testing (for performance and learning ability) of dietarily restricted compared to control mice in relation to age. 5. Morphologic studies: particularly brain morphology; also, tumor patterns and fine structure of endocrine glands, kidneys, and liver.